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Probing dynamic conformational changes in lipid signalling using hydrogen deuterium exchangemass spectrometry

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Most cellular responses to extracellular stimuli have a common component of regulation arising from selective recruitment of a network of signalling complexes to membranes.  However, studying these systems remains a daunting task.  We have made unprecedented progress in understanding these systems by applying a synthesis of hydrogen deuterium exchange mass spectrometry (HDX-MS), X-ray crystallography and FRET spectroscopy. Our application of this synthesis to phosphoinositide 3-kinase (PI3K) signalling represents one of the largest (> 200 kDa) complexes studied using DXMS , and elucidates novel aspects of PI3K regulation downstream of GPC Rs as well as a unifying mechanism of how diverse oncogenic PI3K mutants upregulate activity.

This talk is part of the Experimental and Computational Aspects of Structural Biology and Applications to Drug Discovery series.

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